Life 2.0: a comprehensive cross-sectional profiling of long-term allogeneic hematopoietic cell transplantation survivors compared to a matched general population cohort
Related Articles
The 2023 EBMT report on hematopoietic cell transplantation and cellular therapies. Increased use of allogeneic HCT for myeloid malignancies and of CAR-T at the expense of autologous HCT
In 2023, 47,731 HCT (20,485 (42.9%) allogeneic and 27,246 (57.1%) autologous) in 43,902 patients were reported by 696 European centers. 6042 patients received advanced cellular therapies, 4888 of which were CAR-T. Compared to the previous year there was an increase in CAR-T (+52.5%), in allogeneic HCT (+7.8%) but none in autologous HCT (+0.4%). Main indications for allogeneic HCT were myeloid (11,748; 60.7%), lymphoid malignancies (4,850; 25.0%), and non-malignant disorders (2558; 13.2%). Use of allogeneic HCT increased for AML (+12.1%) and for NHL (+11.0%), particularly in T-NHL (+25.6%). Main indications for autologous HCT were lymphomas (7890; 32.2%), PCD (14,271; 58.2%), and solid tumors (1608; 6.6%) with recovering numbers for autoimmune diseases. In patients with allogeneic HCT, the use of sibling donors increased by +1.0%, haploidentical donors by +11.7%, and unrelated donors by +11.1%. Cord blood HCT decreased again by −5.4%. Pediatric HCT activity increased slightly (5455; +0.1%) with differences between allogeneic (4111; −0.5%) and autologous HCT (1344: +1.7%). Use of CAR-T increased to a cumulative total of 13,927 patients including patients treated for autoimmune diseases. Overall, numbers show a complete recovery from the pandemic dip with increased cellular therapy at the expense of autologous HCT. Allogeneic HCT activity focuses on myeloid malignancies.
Epidemiology of multimorbidity in childhood cancer survivors: a matched cohort study of inpatient hospitalisations in Western Australia
Childhood cancer survivors (CCS) experience an elevated burden of health complications, underscoring the importance of understanding the patterns of multimorbidity to guide the management of survivors with complex medical needs.
Donor MHC-specific thymus vaccination allows for immunocompatible allotransplantation
Organ transplantation is the last-resort option to treat organ failure. However, less than 10% of patients benefit from this only option due to lack of major histocompatibility complex (MHC)-matched donor organs and 25%–80% of donated organs could not find MHC-matched recipients. T cell allorecognition is the principal mechanism for allogeneic graft rejection. We herein present a “donor MHC-specific thymus vaccination” (DMTV) strategy to induce T cell tolerance to both autologous and allogeneic donor MHC. Allogeneic MHC molecules were expressed in the recipient thymus through adeno-associated virus-mediated delivery, which led to stable expression of allogeneic MHC together with the autologous MHC in the engineered thymus. During local T cell education, those T cells recognizing either autologous MHC or allogeneic MHC were equally depleted. We constructed C57BL/6-MHC and BALB/c-MHC dual immunocompatible mice via thymus vaccination of C57BL/6-MHC into the BALB/c thymus and observed long-term graft tolerance after transplantation of C57BL/6 skin and C57BL/6 mouse embryonic stem cells into the vaccinated BALB/c mice. We also validated our DMTV strategy in a bone marrow, liver, thymus (BLT)-humanized mouse model for immunocompatible allotransplantation of human embryonic stem cells. Our study suggests that the DMTV strategy is a potent avenue to introduce a donor compatible immune system in recipients, which overcomes the clinical dilemma of the extreme shortage of MHC-matched donor organs for treating patients with end-stage organ failure.
Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells
Hematopoietic stem and progenitor cells (HSPCs) are critical for the treatment of blood diseases in clinic. However, the limited source of HSPCs severely hinders their clinical application. In the embryo, hematopoietic stem cells (HSCs) arise from hemogenic endothelial (HE) cells lining the major arteries in vivo. In this work, by engineering vascular niche endothelial cells (VN-ECs), we generated functional HSPCs in vitro from ECs at various sites, including the aorta-gonad-mesonephros (AGM) region and the placenta. Firstly, we converted mouse embryonic HE cells from the AGM region (aHE) into induced HSPCs (iHSPCs), which have the abilities for multilineage differentiation and self-renewal. Mechanistically, we found that VN-ECs can promote the generation of iHSPCs via secretion of CX3CL1 and IL1A. Next, through VN-EC co-culture, we showed that placental HE (pHE) cells, a type of extra-embryonic HE cells, were successfully converted into iHSPCs (pHE-iHSPCs), which have multilineage differentiation capacity, but exhibit limited self-renewal ability. Furthermore, comparative transcriptome analysis of aHE-iHSPCs and pHE-iHSPCs showed that aHE-iHSPCs highly expressed HSC-specific and self-renewal-related genes. Moreover, experimental validation showed that retinoic acid (RA) treatment promoted the transformation of pHE cells into iHSPCs that have self-renewal ability. Collectively, our results suggested that pHE cells possess the potential to transform into self-renewing iHSPCs through RA treatment, which will facilitate the clinical application of placental endothelial cells in hematopoietic cell generation.
A mixed studies systematic review on the health and wellbeing effects, and underlying mechanisms, of online support groups for chronic conditions
This pre-registered systematic review aimed to examine whether online support groups affect the health and wellbeing of individuals with a chronic condition, and what mechanisms may influence such effects. In September 2024, literature searches were conducted across electronic databases (Medline, Embase, PsycInfo, Web of Science and Google Scholar), pre-publication websites (MedRxiv and PsyArXiv) and grey literature websites. Qualitative and quantitative studies were included if they explored the impact of online support groups on the health and wellbeing outcomes of individuals with a chronic condition. The Mixed Methods Appraisal Tool was used to appraise the quality of the included studies. In total 100 papers met the inclusion criteria with their findings presented in a thematic synthesis. Health and wellbeing outcomes were categorised as: physical health, mental health, quality of life, social wellbeing, behaviour and decision-making, and adjustment. Mechanisms reported in these studies related to exchanging support, sharing experiences, content expression, and social comparison. User and group characteristics were also explored. The included studies suggest that online support groups can have a positive impact on social wellbeing, behaviour, and adjustment, with inconclusive findings for physical health and quality of life. However, there is also the possibility of a negative effect on anxiety and distress, particularly when exposed to other group members’ difficult experiences. Research comparing different online group features, such as platforms, size, and duration is needed. In particular, future research should be experimental to overcome the limitations of some of the cross-sectional designs of the included studies. The review was funded by the National Institute for Health and Care Research Health Protection Research in Emergency Preparedness and Response. Pre-registration ID: CRD42023399258
Responses